A prospective, randomized phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma

BACKGROUND, A prospective, multicenter, randomized, Phase pi trial comparin g the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin , and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubi cin (NA) in the treatment of patients with advanced breast carcinoma was un dertaken. METHODS, One hundred and seventy-seven patients who previously were untreat ed for recurrent or metastatic breast carcinoma were entered into the study ; 7 patients could not be assessed. The final analysis relates to 85 patien ts who were treated with FAC and 85 patients who were treated with NA, of w hom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemot herapy. RESULTS. The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response ra te (ORR) for FAC was 74% (95% confidence interval [95% CI], 65-83%), and th e ORR for NA was 75% (95% CI, 66-84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overal l survivals were similar, with a median of 17.3 months for patients receivi ng FAC and 17.8 months for patients receiving NA. Severe toxicity was uncom mon with World Health Organization Grade 3-4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incid ence of mild to moderate constipation, neurotoxicity, and phlebitis, wherea s FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS. The efficacy of these two regimens is very similar, although N A may be more active in a subset of patients with visceral metastatic disea se, particularly liver involvement. It is clear that, in a direct compariso n with an established three-drug regimen, the newer two-drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3- 4 toxicity. Cancer 1999;85:1091-7. (C) 1999 American Cancer Society.